Effects of arachidonic acid, monohydroxyeicosatetraenoic acid and prostaglandins on the release of mucous glycoproteins from human airways in vitro.
Human lung explants maintained in culture for 7 d incorporate [(3)H]glucosamine into mucous glycoproteins. Ethanol-precipitable, glucosamine-labeled mucous secretion was measured, and the effects of different pharmacologic agents upon this secretion were investigated. Anaphylaxed human lung generates prostaglandin (PG) synthesis and increased mucous release. Arachidonic acid (AA), PGA(2), PGD(2), and PGF(2alpha) significantly increased mucous glycoprotein release, whereas PGE(2) significantly reduced release. Evidence which suggests that lipoxygenase products of AA augment mucous release includes the following: (a) Nonsteroidal anti-inflammatory drugs (NSAID: acetylsalicylic acid and indomethacin) increase mucous release while preventing prostaglandin formation. (b) The increase in mucous release induced by AA or NSAID is additive once the agents are combined. (c) Several nonspecific lipoxygenase inhibitors (eicosa-5,8,11,14-tetraynoic acid; vitamin E; nordihydroguaiaretic acid; and alpha-naphthol) inhibit mucous release. Three additional lines of evidence directly indicate that monohydroxyeicosatetraenoic acid (HETE) causes increased mucous release: (a) the addition of a mixture of synthetic HETE (24-600 nM) increases mucous release; (b) pure 12-HETE (1-100 nM) also increases mucous release; (c) mucous release is increased synergistically by the combination of HETE and NSIAD. These data taken together demonstrate that HETE are capable of increasing mucous release and that conditions which may influence HETE production alter mucous release. Thus, although not directly demonstrating HETE production by human airways, the data strongly suggest that lipoxygenase products of AA in airways may profoundly influence mucous release; and it seems possible that lipoxygenase inhibitors may have a role in treating bronchorrhea.
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology*; D001982:Bronchial Diseases / Q000188:drug therapy / Q000378:metabolism; D046508:Culture Techniques; D004357:Drug Synergism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D016859:Lipoxygenase Inhibitors; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D009093:Mucus / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D006023:Glycoproteins; D016859:Lipoxygenase Inhibitors; D011453:Prostaglandins; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid